KSR1 Antibody
Description
Cancer Biology
KSR1 antibodies have been instrumental in elucidating its role in oncogenic transformation:
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Melanoma: CRISPR/Cas9-mediated KSR1 knockout in BRAF-mutant melanoma cells reduced proliferation, increased apoptosis, and impaired 3D tumor growth .
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Colorectal Cancer: KSR1 depletion decreased EPSTI1 protein levels, a marker of epithelial-mesenchymal transition, via ERK-dependent translational regulation .
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Small-Cell Lung Carcinoma: KSR1 knockout reduced tumor-initiating cell frequency and sensitized cells to cisplatin .
Immune Regulation
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NK/T Cells: KSR1-deficient natural killer (NK) cells showed impaired cytolytic granule polarization and ERK recruitment to immunological synapses .
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Inflammatory Bowel Disease: KSR1 deficiency exacerbated colitis in Il10−/− mice by enhancing IFN-γ production in T cells .
DNA Damage Response
KSR1 antibodies validated its necessity for ERK activation post-DNA damage (e.g., UV, mitomycin C). Cells lacking KSR1 failed to re-enter the cell cycle after G2/M arrest .
Immunogen and Epitopes
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AF7917: Derived from residues near the C-terminus of human KSR1 (UniProt: Q8IVT5) .
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Post-Translational Modifications (PTMs):
KSR1 undergoes phosphorylation, ubiquitination, and acetylation at specific residues (see table below) :
| Residue | PTM Type | Functional Implication |
|---|---|---|
| S406 | Phosphorylation | Linked to MAP3K7/NME1 signaling |
| Y552 | Phosphorylation | Modulates scaffold activity |
| K656, K709 | Acetylation | Regulatory roles in ERK signaling |
Validation Data
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WB Specificity: AF7917 detects a 120 kDa band in human and mouse lysates, while ab68483 shows a 110 kDa band in human tissues .
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IHC Reliability: ab68483 demonstrated strong nuclear/cytoplasmic staining in cervical carcinoma FFPE sections .
Key Findings from KSR1 Antibody Studies
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Scaffold vs. Kinase Activity: KSR1 exhibits dual roles as a scaffold and functional kinase, autophosphorylating serine residues and phosphorylating MEK1 to regulate TNF-induced cell survival .
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Concentration-Dependent Signaling: Optimal KSR1 expression (14× endogenous levels) maximizes ERK activation and proliferation, while overexpression inhibits signaling .
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Therapeutic Potential: KSR1 knockout mice resist Ras-driven tumorigenesis, highlighting its viability as a drug target .
Product Specs
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Target Background
- Research findings indicate that KSR-MEK complexes allosterically activate BRAF through interactions involving the N-terminal regulatory region and kinase domain. These findings challenge the conventional understanding of KSR's role as a scaffold for MEK recruitment to RAF. PMID: 29433126
- Homozygous deletion of KSR1 in a mouse model of RAS-driven pancreatic cancer mitigated morbidity but did not completely prevent tumor development. PMID: 29596465
- Praja2 regulates KSR1 stability and mitogenic signaling. PMID: 27195677
- Data demonstrate that neurofibromin 2 (Merlin) suppresses proliferation and adhesion, at least partially, by inhibiting kinase suppressor of Ras 1 (KSR1) and DCAF1 protein. PMID: 26549023
- Evidence suggests that Rap1 activation of ERKs requires PKA phosphorylation and KSR binding. PMID: 28003362
- Upregulation of KSR1 is associated with Colorectal cancer. PMID: 26673620
- The relative mRNA copy values of KSR1, ERK1 and ERK2 in cancer tissues were 2.43 +/- 0.49, 2.10 +/- 0.44 and 3.65 +/- 0.94. EGb 761 enhanced the chemotherapy sensitivity through suppression of the KSR1-mediated ERK1/2 pathway in gastric cancer. PMID: 25962735
- KSR1 rs2241906 variants may predict survival in patients with advanced ERalpha+ BC treated with adjuvant TAM. PMID: 25287073
- KSR1 is coordinately regulated with Notch signaling and oxidative phosphorylation in papillary thyroid cancer. PMID: 25608512
- KSR1 stabilizes BRCA1 by reducing BRCA1 ubiquitination, inhibits tumor growth through BRCA1, and regulates BRCA1 stability via elevated BARD1 abundance and increased BRCA1-BARD1 interaction. PMID: 24909178
- Data suggest that caveolin-1 is essential for optimal KSR1-dependent ERK activation by growth factors and oncogenic Ras. PMID: 25002533
- Research indicates that phosphorylation of BRAF by AMPK disrupts its association with KSR1. PMID: 24095280
- Our findings integrate KSR1 into a network involving DBC1 and SIRT1, which results in the regulation of p53 acetylation and its transcriptional activity. PMID: 24129246
- Elevated levels of phosphorylated KSR were detected in the nuclear fractions. PMID: 23416464
- The atypical C1 domain, the CC-SAM domain is required to target KSR-1 to the plasma membrane. PMID: 23250398
- Simulations provide a multi-dimensional exploration of how EGF-dependent EGFR endocytosis and ERK activation are dynamically affected by scaffolds KSR and MP1, co-regulated by Cbl-CIN85 and Endophilin A1. PMID: 21829671
- Genetic disruption of the scaffolding protein, Kinase Suppressor of Ras 1 (KSR1), differentially regulates GM-CSF-stimulated hyperproliferation in hematopoietic progenitors expressing activating PTPN11 mutants D61Y and E76K. PMID: 21555152
- Oncoprotein Cot1 represses kinase suppressors of Ras1/2 and 1,25-dihydroxyvitamin D3-induced differentiation of human acute myeloid leukemia cells. PMID: 20945381
- KSR1 kinase activity is essential for anti-apoptotic protection of the intestinal epithelium [review]. PMID: 15520853
- KSR1-mediated regulation of ERK activity represents a novel determinant of CDDP sensitivity of cancer cells. PMID: 15899786
- 1,25D selectively increases the expression of the gene encoding kinase suppressor of Ras-1 (KSR-1) in HL60 cells. PMID: 16732322
- Human KSR1 proteins promote assembly of multivalent Raf.MEK complexes that are required for c-Raf kinase activation and functional coupling of active kinases to downstream substrates. PMID: 18332145
- Down-regulation of KSR1 in pancreatic cancer xenografts by antisense oligonucleotide correlates with tumor drug uptake. PMID: 18719367
- KSR1 regulated the threshold required for MAPK activation in T cells without affecting the nature of the response. PMID: 19188442
- DC-SIGN was constitutively associated with a signalosome complex consisting of the scaffold proteins LSP1, KSR1 and CNK and the kinase Raf-1. PMID: 19718030
